Impact of subsequent immune checkpoint inhibitor treatment on overall survival with avelumab vs docetaxel in platinum-treated advanced NSCLC: Post hoc analyses from the phase 3 JAVELIN Lung 200 trial

Objectives: The JAVELIN Lung 200 phase 3 trial did not meet its primary endpoint of improving overall survival (OS) with avelumab vs docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report post hoc analyses assessing the effects of subsequent immune checkpoint inhibitor (ICI) treatment on OS. Material and methods: Patients with stage IIIB/IV NSCLC progressed following platinum-doublet therapy were randomized to receive avelumab or docetaxel. OS was analyzed in the PD-L1+ population (≥1% of tumor cells) and full analysis set (PD-L1+ or PD-L1−). Effects of subsequent ICI (after permanent discontinuation of study treatment) on OS were analyzed using a preplanned naive sensitivity analysis and post hoc inverse probability of censoring weighting (IPCW) analysis. Subgroups with or without subsequent ICI treatment were analyzed using descriptive statistics. Results: In the avelumab and docetaxel arms, a subsequent ICI was received by 16/396 (4.0 %) and 104/396 (26.3 %) after a median of 10.5 months (range, 3.9–20.4) and 5.7 months (range, 0.1–24.4), respectively. Some subgroups showed trends for higher subsequent ICI treatment, including patients with non-squamous NSCLC (avelumab arm, 4.3 % vs docetaxel arm, 32.1 %) or with a baseline ECOG performance status of 0 (6.3 % vs 31.3 %); those enrolled in the early recruitment wave (11.6 % vs 54.3 %), or enrolled in the US/Western Europe (2.8 % vs 45.5 %) or Asia (11.0 % vs 35.4 %); and non-white patients (10.1 % vs 35.0 %). The hazard ratio for OS with avelumab vs docetaxel was lower in the IPCW analysis than in the naive sensitivity analysis (PD-L1+ population: 0.80 [95 % CI, 0.62−1.04] vs 0.86 [95 % CI, 0.68−1.09], respectively). Conclusion: In the JAVELIN Lung 200 trial, avelumab showed clinical activity as second-line treatment for patients with advanced NSCLC. Post hoc analyses suggest that the primary OS analysis may have been confounded by subsequent ICI use in the docetaxel arm. ClinicalTrials.gov identifier: NCT02395172.